Low‐dose provocation and skin tests in patients with hypersensitivity to gadolinium‐based contrast agents

Abstract

Reported reaction rates with gadolinium-based contrast agents (GBCA) ranged from 0.07% to 2.4%, the rate of hypersensitivity reaction (HS) is around 0.1% 1 and immediate and delayed HS have been reported. [1][2][3][4] The diagnosis of HS to GBCA is challenging, based on clinical history and skin tests. Although little data are available on the performances of the GBCA skin tests, its negative predictive value appears to be of interest. 5 Some classes of GBCA had been commercialized, grouped according their chemical structures and properties: macrocyclic or linear and ionic or non-ionic GBCA; some linear GBCA called protein-binding agents had briefly bound serum albumin or other proteins. A recent systematic review and meta-analysis reported that a higher rate of immediate HS was associated with ionicity, protein binding, and macrocyclic structure of GBCA. 6 From 2004 to 2009, the FDA received reports on 40 gadoliniumbased contrast agent U.S. deaths unrelated to nephrogenic systemic fibrosis, with an incidence per million doses of 0.15, 0.19, 0.97, 2.7, and 0.7 for gadodiamide, gadoversetamide, gadopentetate dimeglumine, gadobenate dimeglumine, and gadoteridol, respectively. 2The aim of this retrospective study was to evaluate the performances of skin tests and an intravenous provocation test (IPT) with low-dose GBCA in patients with suspected HS to GBCA.We report an observational retrospective study, in accordance with local ethics committee. We enrolled all patients with a history of HS to GBCA who underwent skin tests and IPT with low-dose GBCA between January 2013 and December 2015. Skin tests were performed following the EAACI-ENDA recommendations. 7 Briefly, skin prick tests (PTs) involved undiluted GBCA commercial solutions, and, when negative, were followed by intradermal tests (IDTs) successively with 100-fold and/or 10-fold solution diluted in 0.9% sterile saline. Readings were performed at 20 minutes, and at Day 2 in case of delayed HS. After signed informed consent from the patient, a single-blind placebo-controlled IPT, during 8-hours hospital stay with 1 mL of the GBCA solution (corresponding to one tenth of the usually injected GBCA for magnetic resonance imaging [MRI]), was proposed with gadoteric acid, if the skin test result remained negative, and with another GBCA if the patient requested a particular GBCA. The IPT result was considered positive for immediate HS if oxygen saturation decreased below 90% and/or a skin eruption (urticaria, angioedema or maculopapular rash) occurred up to 2 hours after the challenge and a skin eruption occurred between 2 hours and up to 7 days after the challenge for delayed HS.Fourteen patients had skin tests and IPT with GBCA; 12 of them had immediate HS, one a delayed HS, and one could not be classified due to missing information. The severity of the immediate HS was grade I and grade II according to Ring and Messmer severity classification, for respectively four and eight out of 12 patients and one delayed HS occurred with exanthema and dyspnoea more than 6 h...

Assessment of immediate and non-immediate hypersensitivity contrast reactions by skin tests and provocation tests: A review

“…In the case of IHR with positive skin tests, a provocation was performed with an alternative gadolinium-based contrast medium and a negative skin test: all provocations were negative. 35 – 38 …”

Subsequent MRI of pediatric patients after an adverse reaction to Gadolinium-based contrast agents

“…Based on our experience, the intravenous provocation test led to a remarkable reduction of concerns in patients, parents and radiologists, probably due to the better simulation of the real-life situation and uneventful subsequent MRI examinations with a tested GBCA. In a recent study, the experience with an intravenous provocation test with which to rule out a GBCA associated allergic reaction in adult patients was reported [18].…”

“…To our knowledge, there are two reported experiences about intravenous provocation testing to rule out GBCA-associated allergic reactions [18] and iodine contrast agent-associated allergic reactions in adult patients [19].…”

Adverse reactions during procedures

“…Intravenous drug provocation test (DPT) with a skin testenegative contrast agent (ICM or GBCM) has been increasingly described, but it is neither part of routine allergological workup yet nor standardized and validated. 39,59,[61][62][63][64] For fluorescein, conjunctival DPT has been reported as additional diagnostical step when all skin tests were negative. 65 Severe reactions to DPT have been reported, and DPT could cause side effects such as kidney damage when using ICM or nephrogenic systemic fibromatosis when using GBCM.…”